Synthesis and Characterization of 9-Phenyl-9H-purin-6-amines from 5-Amino-1-phenyl- 1H-imidazole-4-carbonitriles

Transcription

1 ISS: ; CODE ECJAO E Chemistry Vol. 4, o. 3, pp , July 2007 Synthesis and Characterization of 9Phenyl9purin6amines from 5Amino1phenyl 1imidazole4carbonitriles ASIE YAYAZADE* and FATEMA ABIBI Department of Chemistry, University of Guilan, P.O. Box 1914, asht, Iran. yahyazadehphd@yahoo.com eceived 13 December 2006; Accepted 10 January 2007 Abstract: 9Phenyl9purin6amine derivatives have been synthesized in high yields by reaction between 5amino1phenyl1imidazole4 carbonitrile with C(OEt) 3 and Ac 2 O followed by reaction with ammonia. Keywords : Imidazole, 9Phenyl9purin6amine, Purine, Formimidate, Formamidine Introduction Purines are a class of heterocyclic compounds which play an important role in many biological processes 15. The most important natural occurrence of purines is in the nucleotides and nucleic acids; compounds which perform some of the most crucial functions in fundamental metabolism. The chemotherapeutic uses of purines and purine analogues have prompted tremendous efforts towards their synthesis, both in academia and in the pharmaceutical industry 69. As the purine ring system is a fusion of two aromatic heterocyclces, pyrimidine and imidazole, a logical starting point for ring synthesis is an appropriately substituted pyrimidine or imidazole from which the second ring can be constructed by a cyclization process 10,11. Experimental All solvents purified and dried using established procedures. The 1 M spectra were recorded on itachiperkinelmer 24B (60 Mz) or Bruker XL 300 (500 Mz) instruments

2 373 ASIE YAYAZADE et al. (with Jvalues given in z), 13 C M spectra either on a Bruker WP 80 or XL300 instrument, and I spectra on a Shimadzu I435 spectrophotometer. Mass spectra were recorded on a Kratos Concept instrument. The melting points were measured on an Electrothermal digital melting point apparatus and are uncorrected. General procedure for the preparation of 1aryl4cyano5[(ethoxymethylene)amino]imidazoles (4ab) A mixture of 5amino1aryl4cyanoimidazole (0.5 g), triethyl orthoformate (12.0 M equivalent), and acetic anhydride (6.0 M equivalent) was heated gently at C under an argon atmosphere for several hours. After TLC showed that no starting material remained the resulting yellowbrown solution was evaporated under vacuum to give a residue which, upon treatment with a mixture of dry diethyl ether / hexane (1:1) afforded a precipitate which was filtered off, washed with the same mixture and dried under vacuum to give the products 4ab. General procedure for the preparation of 9aryl6aminopurines (5ab) To a stirred solution of the 1aryl4cyano5[(ethoxymethylene)amino]imidazole (4ab) (0.3 g) in dry methanol (810 cm 3 ) under an argon atmosphere at room temperature was added amonnia (1M equivalent). After 1520 minutes, the separated precipitate was filtered off, washed with a mixture of dry diethyl ether/hexane (1:1), and dried under vacuum to give 5ab. esults and Discussion 5amino4cyanoimidazoles are useful intermediates for purine synthesis 12. There are few reports of 9aminopurine derivatives and most of the routes described are from 5amino4 hydrazinopyrimidine precursors, substituted in the 2 and 6position We therefore decided to investigate the reactions of 9phenyl9purin6amines 5ab were prepared via a multistep synthesis from ethyl (Z)(2amino1,2 dicyanovinyl)formimidate (1), by treatment with a phenylamine in a 1:1 molar ratio in ethanol in the presence of a catalytic amount of aniline hydrochloride to give the corresponding formamidine 16, 17 (Scheme 1). Cyclisation of the formamidines in the presence of a strong base, aqueous KO solution, provided the corresponding 5amino1phenyl1imidazole4carbonitriles (3ab), 9,10 which are readily converted to 9phenyl9purin6 amines (5ab) by treatment with C(OEt) 3 and Ac 2 O followed by reaction with ammonia (Scheme 2). OEt 2 C C i ii 2 C iii 2 C 2 C C 2 C 1 2ab 3ab a : =4BrC 6 4 b : =4FC 6 4 Scheme 1. eagents and conditions: (i) C(OEt) 3, dioxane, heat; (ii) 2, Ph + 3 Cl, room temp., 34h; (iii) 1mol KO aq. room temp.

3 Synthesis and Characterization 374 The initial step involved conversion of the 5amino4cyanoimidazoles (3) to the corresponding ethoxyimidates (4). These were prepared by heating the appropriate cyanoamine with triethyl orthoformate and acetic anhydride on a water bath at 6080 o C for several hours (Scheme 2). Once TLC confirmed complete consumption of the starting material, the result in solution were evaporated under vacuum to give a residue that upon treatment with a mixture of dry diethyl ether and hexane (1:1), gave the required imidates 4a and 4b as a solid in 81 87% respectively yield. The products were recrystallised from a mixture of dry diethyl ether and hexane (1:1). In the infrared spectra the presence of the cyano and C= stretching vibrations were observed in the range of and cm 1 respectively. The 1 M spectra of the isolated ethoxyimidates (4ab) showed the presence of the 2 proton of the imidazole ring in the range of δ ppm. The 7 proton appeared in the range δ ppm. The C 2 and C 3 of the ethoxy group had clear quartet and triplet patterns as expected in the regions of δ and δ ppm respectively. The other bands were in agreement with expected structures. The 13 C M spectra of the imidazoles had the expected number of bands with the C2 carbon of the imidazole ring in the region of δ , the C7 carbon at δ and the C4 carbon within the region of δ ppm. The imidates (4ab) were converted to the corresponding 9phenyl9purin6 amines (5ab) by treatment with ammonia in the minimum amount of methanol. The reaction was carried out under an argon atmosphere at room temperature. During the first 20 minutes a white precipitate started to form. After 23 h TLC showed no staring material, and filtration of the reaction mixture gave the purines as a powder in 6783% yield. The purines (5ab) were fully characterized by microanalysis and spectroscopic methods. 3ab iv 4ab C C(OEt) ab a : =4BrC 6 4 b : =4FC 6 4 Scheme 2. eagents and conditions:(iv) C(OEt) 3, (C 3 CO) 2 O, heat, (v) 3, MeO, heat. The elemental analysis and mass spectra of isolated 9phenyl9purin6amines (5ab) were satisfactory. In the infrared spectra, the stretching vibrations were observed as 23 bands in the range of and C= absorption band in the range cm 1. The 2 protons were observed in the range δ ppm, the proton at position 2 of the purines system appeared in the regions of δ ppm and the proton at position 8 were seen as a singlet in the range of δ ppm. The 13 C M spectra of the compounds (5ab) had the expected number of peaks. The C8 carbon of the imidazoles ring appeared in the region of ppm. The carbon at positions C2 and C6 of the purines system appeared at δ and ppm respectively. v 2

4 375 ASIE YAYAZADE et al. Acknowledgments We are thankful to the Guilan University esearch Council for the partial support of this work. eferences 1 Booth B L, Dias A D and Proenca M F, J. Chem. Soc. Perkin. Trans. 1, 1992, Booth B L, Freitas A P, Fernanda M and Proenca J P, J. Chem. esearch (S), 1993, uryn D M and Okabe M, AidsDriven nucleoside Chemistry, 1992, 92, Erian A W, Chem. ev. 1993, 93, Asano S, Itano K, Yamagata Y and Kohda K, ucleosides & ucleotides. 1994, 13, Birkett P and King, Tetrahedron, 1993, 49, Ohtsuka Y, J. Org. Chem. 1979, 44, Moriya O, Synth. Commun. 1984, Yahyazadeh A, uss. J. Org. Chem. 2003, 39, Yahyazadeh A, Pourrostam B and abiee M, Bull. Korean. Chem. Soc. 2003, 24, Booth B L, Alves M J, Carvalho A, Eastwood P and ezhat L, J. Chem. Soc. Perkin. Trans. 1994, 2, Yahyazadeh A and Booth B L, Synth. Commun. 2001, 31, Yahyazadeh A and Sharifi Z, Phosphorus, Sulfur, and Silicon. 2006, 6, Yahyazadeh A and Booth B L, Synth. Commun. 2002, 21, Booth B L, Alves M J, Proenca J P and Fernanda M, J. Chem. Soc. Perkin. Trans. 1, 1990, AlAzmi A, Elassar A A and Booth B L, Tetrahedron,.2003, 59, AlAzmi A, Elassar A A, Booth B L, Carpenter A, Carvalho A and Marrelec E, J. Chem. Soc. Perkin. 1, 2001, 2532.

5 Medicinal Chemistry indawi Publishing Corporation Photoenergy Organic Chemistry International indawi Publishing Corporation indawi Publishing Corporation Analytical Chemistry indawi Publishing Corporation Advances in Physical Chemistry indawi Publishing Corporation Carbohydrate Chemistry indawi Publishing Corporation Quantum Chemistry indawi Publishing Corporation Submit your manuscripts at The Scientific World Journal indawi Publishing Corporation Inorganic Chemistry indawi Publishing Corporation Theoretical Chemistry Catalysts indawi Publishing Corporation Electrochemistry indawi Publishing Corporation Chromatography esearch International indawi Publishing Corporation indawi Publishing Corporation Spectroscopy indawi Publishing Corporation Analytical Methods in Chemistry indawi Publishing Corporation Applied Chemistry indawi Publishing Corporation Bioinorganic Chemistry and Applications indawi Publishing Corporation Chemistry indawi Publishing Corporation Spectroscopy indawi Publishing Corporation